The amino acid L-valine is used in human medicine, in the pharmaceutical industry, in the food industry as well as in pet food.
It is known that amino acids are produced from the fermentation of strains of coryneform bacteria, particularly corynebacterium glutamicum. Due to their great importance, the manufacturing processes are continually improved. Manufacturing improvements can relate to fermentation measures, such as agitation and supply with oxygen for example, or to the composition of the nutrient solutions, such as the glucose concentration during fermentation, or the processing into the product form, for example through ion exchange chromatography or the intrinsic performance characteristics of the microorganism itself.
Methods of mutagenesis, selection, and mutant selection are used to improve the performance characteristics of these microorganisms. By doing so, strains are obtained that are resistant to anti-metabolites or that are auxotrophic for regulatory significant metabolites and produce L-amino acids. Such a corynebacterium strain is described, for example in the U.S. Pat. No. 5,521,074, which strain is resistant to L-valine and sensitive to fluoropyruvic acid. Furthermore, it is described in EP 0287123 that corynebacteria with resistance to mycophenolic acids can be used advantageously for L-valine production. From EP 0519113 A1 and U.S. Pat. No. 5,658,766 it is also known that the mutants with mutated valyl-tRNA synthetase in combination with further mutations can be used for L-valine production. In addition, WO 001996006926 A1 describes a process for the production of L-valine, wherein a microorganism is used that requires the vitamin lipoic acid for growth and has a defect in the ATPase.
Recombinant DNA technology is additionally used for improving the intrinsic characteristics of L-amino acids-producing strains of corynebacterium. The documents EP 1155139B1 and EP 0356739 B1, for example, describe that the enhancement of the expression of the biosynthesis genes ilvBN, ilvC, and ilvD is advantageously used for the production of L-valine. Furthermore, it is known from EP 1155139 B1 that for L-valine production the weakening or elimination of the threonine dehydratase gene ilvA and/or of genes of the pantothenate synthesis can be used.